Cesium fluoride → HCID 46897012, compound

HRID 242022Notes

Reaction equation

HRID 242022 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])[C:21](=[O:22])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:35]1[N:36]=[CH:37][S:38][CH:39]=1)CCC.[F-].[Cs+]>CN(C)C=O.C(OCC)(=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[N:10][N:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([C:35]4[N:36]=[CH:37][S:38][CH:39]=4)=[CH:3][CH:4]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 27632584-(Tri-n-butylstannyl)thiazoleHCID 468966115-[(6-Bromopyridin-3-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 46897012HCID 46897012, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-[(6-Bromopyridin-3-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 22), 77 mg, 0.17 mmol] and 4-(tributylstannyl)thiazole (77 mg, 0.21 mmole, 1.2 equiv) were dissolved in degassed N,N-dimethylformamide (1 mL) and treated with cesium fluoride (52 mg, 0.34 mmol, 2 equiv), copper(I) iodide (13 mg, 0.069 mmol, 0.4 equiv), and tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.035 mmol, 0.2 equiv). The mixture was stirred at ambient temperature for one hour, diluted with ethyl acetate (15 mL) and filtered. The filtrate was concentrated in vacuo and the residue was purified by preparative reverse phase HPLC (15:85 to 65:35; acetonitrile containing 0.01% trifluoroacetic acid:water containing 0.01% trifluoroacetic acid), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 9.13 (1H, s), 8.95 (1H, s), 8.50 (1H, s), 8.35 (2H, br d, J=7.9 Hz), 8.08 (1H, d, J=8.5 Hz), 7.73-7.60 (3H, m), 7.45 (1H, br s), 7.39-7.31 (3H, m), 5.97 (2H, s), 2.73 (3H, s) ppm; low resolution mass spectrometry (ES+) m/z 451.3 [(M+H)+; calculated for C25H19N6OS: 451.3].

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by preparative reverse phase HPLC (15:85 to 65:35; acetonitrile containing 0.01% trifluoroacetic acid:water containing 0.01% trifluoroacetic acid)

Sources & evidence

ORD record
ord-17e5bb14624d463bacee5a6ece763d8f
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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